1. Field of the Invention
The present invention relates to sensing of bioprocess parameters and, more particularly, non-invasive sensing of bioprocess parameters.
2. Background of the Related Art
Bioprocesses are important in a wide variety of industries such as pharmaceutical, food, ecology and water treatment, as well as to ventures such as the human genome project (Arroyo, M. et al., Biotechnol. Prog. 16: 368-371 (2000); Bakoyianis, V. and Koutinas, A. A., Biotechnol. Bioeng. 49: 197-203 (1996); Bylund, F. et al., Biotechnol. Bioeng. 69: 119-128 (2000); Handa-Corrigan, A. et al., J. Chem. Technol. Biotechnol. 71: 51-56 (1998); López-López, A. et al., Biotechnol. Bioeng. 63: 79-86 (1999); McIntyre, J. J. et al., Biotechnol. Bioeng. 62: 576-582 (1999); Pressman, J. G. et al., Biotechnol. Bioeng. 62: 681-692 (1999); Yang, J.-D. et al., Biotechnol. Bioeng. 69: 74-82 (2000)).
Most cell cultures are conducted by introducing cells and growth media in some form of sterile plastic container in an incubator. It is desirable to monitor growth parameters of the culture, such as oxygen, pH, pCO2, glucose, ions, etc. Ideally, the measurement should be as non-invasive and contamination free as possible. In this regard, related art non-invasive sensors consist of sterilizable patches that are introduced into the vessel and monitored optically from outside the vessel. These have been extensively described in the literature (V. Vojinovic et al., Sensors and Actuators B 114:1083-1091 (2006); T. Scheper et al., Analytica Chimica Acta 400: 121-134 (1999); V. Vojinovic et al., CI & CEP 13: 1-15 (2007); S. Bambot et al., Biotechnology and Bioengineering 43: 1139-1145 (1994)).
However, the need to introduce sensor patches into the vessel poses some problems. First, the system is not easy to manufacture, as the sensors must be inserted prior to vessel sterilization. This operation can lead to the need to recalibrate the sensors after sterilization. In cases where the sensors are to be introduced into pre-sterilized vessels, it is cumbersome to get the sensors to the right spot. Secondly, there is extensive validation needed as the sensor chemistries are in direct contact with the cell culture media. Furthermore, for long duration experiments, there is no easy means of checking sensor patch calibration or replacing a malfunctioning sensor.